DESCRIPTION: Osteoporosis is a major public health problem in the U.S., causing considerable morbidity and mortality. Bone loss associated with aging occurs in both sexes. However, women are at increased risk of osteoporosis due to the rapid acceleration of bone loss associated with estrogen deficiency following menopause. Estrogen replacement therapy (ERT) is one of the mainstays for the prevention and treatment of osteoporosis in postmenopausal women. However, ERT has a number of undesirable effects including, controversially, a possible increase in the risk of breast cancer. Accordingly, compliance with ERT regimes is low. There is increasing interest in the use of phytoestrogens (plant compounds with structural or functional similarity to estradiol) as a possible alternative to ERT. Soybeans and their products are the principal source of the isoflavones, genistein and daidzein. Several lines of evidence suggest that isoflavones and related compounds may have beneficial skeletal effects, i.e. are acting as estrogen agents. However, nothing is known about the metabolic effects of isoflavones, and specifically, their effects on calcium handling in the body. The aim of this study is to test the hypothesis that soybean isoflavones increase calcium absorption and enhance calcium retention in postmenopausal women. The study design is a randomized, crossover intervention study. Twenty postmenopausal women will be studied three times under different dietary interventions: soy protein enriched with isoflavones; soy protein devoid of isoflavones; and a casein control. Using a combination of metabolic balance methodology, radioisotopic tracer techniques, and biochemical and hormonal measures of bone metabolism, the following parameters will be measured: calcium absorption, calcium excretion, net calcium retention, bone formation, bone resorption, body pool size and calcium turnover rates. This will be the first bone study in humans to distinguish between the effects of isoflavones, and the effects of soy protein per se, on calcium metabolism, i.e. estrogenic versus non-estrogenic metabolism. Elucidation of mechanism of action of isoflavones is essential in order to confirm their effectiveness in the prevention of postmenopausal bone loss. The importance of this work lies in the potential of a simple dietary intervention - increased soy food consumption - to attenuate bone loss without side-effects of ERT. Such information could have important public health consequences for the prevention of osteoporosis.